Construction Of Self-activated NO-releasing Hydrogel And Its Application In Photothermal Synergies Antibacterial Infection

Bacterial infections cause about 10 million deaths per year and have become a serious threat to human life and health.Antibiotic-based therapy is a common strategy in treatment of bacterial infections,but the emergence of multiple drug-resistant bacteria caused by the abuse of antibiotics has made it harder to confront bacterial infections.Therefore,it is urgent to develop new antibiotic-independent therapies to combat bacterial infections.Nitric oxide（NO）,an endogenous signaling molecule involving in a variety of physiological and pathological processes in the human body,could kill bacteria through multiple mechanisms,such as lipid peroxidation,degradation of bacterial DNA and disruption of bacterial membrane integrity.Moreover,it exhibits broad-spectrum antimicrobial activity and is not easy to induce drug resistance.Although NO-based antibacterial strategies show great potential,the biosafety of traditional NO donors,residual toxicity and cumbersome construction of carriers frustrate their wide applications.L-arginine（LA）,one of human essential amino acids with good biological properties,can produce NO under the action of nitric oxide synthase（NOS）in the body.In addition,as a natural NO donor,LA can be oxidized to release NO in the presence of reactive oxygen species（ROS）including H₂O₂ and ¹O₂,possessing broad application prospects.Photothermal therapy（PTT）utilizes specific wavelength laser to activate photothermal conversion agent to locally generate hyperthermia,which could cause functional disturbance of bacterial protein,disruption of the bacterial membrane structure,causing death to bacteria without producing drug resistance.It has aroused much attention in the antibacterial field by the significant advantages of spatiotemporal controllability and non-invasiveness.However,the single PTT strategy often rely on larger doses to fight bacterial infections.Synergistic therapies can achieve high-efficiency eradication of bacteria at lower doses by integrating the advantages of monotherapy and minimizing side effects.The aim of this study was to construct a simple,efficient and biological NO synergistic PTT antibacterial system for bacterial wound infection.Alginate-based hydrogels with excellent biosafety,have been employed in diverse biomedical applications,including wound dressing,tissue repair,and drug delivery.In this study,a self-activated hydrogel（OCL hydrogel）that releases NO was prepared by Ca²⁺-crosslinked sodium alginate doped with Ca O₂ nanoparticles,LA,and oxidized mesoporous carbon nanoparticles（OMCN）for combating bacterial infections in combination PTT.In this system,Ca O₂ could react with water to produce H₂O₂,and locally concentrated H₂O₂ can further oxidize LA to release NO.Meanwhile,thanks to the excellent photothermal effect of OMCN,OCL hydrogel can achieve efficient NO and PTT synergistic bactericidal performance upon the irradiation of 808 nm laser.The antibacterial results in vitro demonstrated that the composite hydrogel had an obvious killing effect on E.coli and S.aureus.Furthermore,the experimental results in vivo showed that OCL hydrogel possessed a good therapeutic effect in treating bacteria-infected wound of back in mice,while appearing no evident biological toxicity during the whole treatment process.In addition,the limited environment of hydrogel made the nanomaterial components easy to be removed from the infected wound,reducing the potential side effects from the residues of the excipients after treatment.In conclusion,the designed OCL hydrogel antibacterial system presents a great prospect for the treatment of bacterial infections.